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Stephen M Strittmatter

Publications and source records attributed to Stephen M Strittmatter.

41 records · Page 3Linked to original sources
PubMed2002

Nogo-66 receptor antagonist peptide promotes axonal regeneration.

Myelin-derived axon outgrowth inhibitors, such as Nogo, may account for the lack of axonal regeneration in the central nervous system (CNS) after trauma in adult mammals. A 66-residue domain of Nogo (Nogo-66) is expressed on the surface of oligodendrocytes and can inhibit axonal outgrowth through an axonal Nogo-66 receptor (NgR). The IN-1 monoclonal antibody recognizes Nogo-A and promotes corticospinal tract regeneration and locomotor recovery; however, the undefined nature of the IN-1 epitope in Nogo, the limited specificity of IN-1 for Nogo, and nonspecific anti-myelin effects have prevented a firm conclusion about the role of Nogo-66 or NgR. Here, we identify competitive antagonists of NgR derived from amino-terminal peptide fragments of Nogo-66. The Nogo-66(1 40) antagonist peptide (NEP1 40) blocks Nogo-66 or CNS myelin inhibition of axonal outgrowth in vitro, demonstrating that NgR mediates a significant portion of axonal outgrowth inhibition by myelin. Intrathecal administration of NEP1 40 to rats with mid-thoracic spinal cord hemisection results in significant axon growth of the corticospinal tract, and improves functional recovery. Thus, Nogo-66 and NgR have central roles in limiting axonal regeneration after CNS injury, and NEP1-40 provides a potential therapeutic agent.

Amino Acid Sequence↗
PubMed2002

Small proline-rich repeat protein 1A is expressed by axotomized neurons and promotes axonal outgrowth.

The ability of neurons to regenerate an axon after injury is determined by both the surrounding environment and factors intrinsic to the damaged neuron. We have used cDNA microarrays to survey those genes induced during successful sciatic nerve regeneration. The small proline-rich repeat protein 1A (SPRR1A) is not detectable in uninjured neurons but is induced by >60-fold after peripheral axonal damage. The protein is localized to injured neurons and axons. sprr1a is one of a group of epithelial differentiation genes, including s100c and p21/waf, that are coinduced in neurons by axotomy. Overexpressed SPRR1A colocalizes with F-actin in membrane ruffles and augments axonal outgrowth on a range of substrates. In axotomized sensory neurons, reduction of SPRR1A function restricts axonal outgrowth. Neuronal SPRR1A may be a significant contributor to successful nerve regeneration.

Actins↗
PubMed2002

Nogo and the Nogo-66 receptor.

Nogo has been identified as a component of central nervous system (CNS) myelin preventing axonal regeneration in the adult vertebrate CNS. Our previous analysis of Nogo-A demonstrated that an axon-inhibiting 66 aa domain is expressed at the extracellular surface and the endoplasmic reticulum lumen of transfected cells and oligodendrocytes. We have identified a brain-specific, leucine-rich repeat protein with high affinity for soluble Nogo-66. Cleavage of the Nogo-66 receptor from axonal surfaces renders neurons insensitive to Nogo-66. Nogo-66 receptor expression is sufficient to impart Nogo-66 axonal inhibition to unresponsive neurons. With identified ligand and receptor components, structure-function determinants for inhibition of axon regeneration can now be mapped. The relative contribution of Nogo, myelin-associated glycoprotein, chondroitin sulfate proteoglycan and oligodendrocyte myelin glycoprotein to myelin inhibition can be assessed. Blockade of Nogo-66 interaction with its receptor provides one potential avenue to promote axonal regeneration after adult mammalian CNS injury.

Animals↗
PubMedDate not supplied

Modulation of axonal regeneration in neurodegenerative disease: focus on Nogo.

Recent work has demonstrated that axonal regeneration in the central nervous system is limited by myelin-derived Nogo binding to an axonal Nogo Receptor. The Nogo system appears to have a physiologic role in regulating structural plasticity. The possibility that the Nogo system contributes to pathologic and compensatory plasticity in Alzheimer's Disease is considered.

Alzheimer Disease↗